{"title":"Structural Revision of the Pyrone Natural Product Syzysamalactone via Synthesis","authors":"Raju Dupud, Dilna Fathima, Sahla Latheef, Sunil Kumar Nechipadappu, Choppari Thirupathi, Remya Ramesh","doi":"10.1021/acs.jnatprod.6c00599","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.6c00599","url":null,"abstract":"<p>The first synthesis of the proposed structure of a neuroprotective natural product, syzysamalactone, was accomplished starting from 4-ethylcyclohexane-1,3-dione. The synthesis features a one-pot Michael addition annulation cascade to 2-pyrone in water as a solvent. The spectral data of the synthetic product did not match the reported data, indicating the need for structural revision. A significant difference in the chemical shift of the carbonyl carbon suggested a 4-pyrone skeleton, which was subsequently confirmed by synthesis. The racemic mixture was resolved by chiral HPLC, and the natural product was assigned the (<em>S</em>, <em>S</em>) configuration by XRD analysis of its 4-nitrobenzoate ester.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"89 9","pages":"2726–2733"},"PeriodicalIF":3.7,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149153114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniel Domingo-Fernández, Patrick Slack, Ifra Saifi, Adam Bayless, William Wen, António Preto, Erik DeBloois, Jennifer Shipp, Tendai Chisowa, August Allen, Daniel Wee, Viswa Colluru, Biswapriya B. Misra, Andrew Katz
{"title":"Chemotaxonomic Map of Labdane Diterpenoids in Acanthaceae","authors":"Daniel Domingo-Fernández, Patrick Slack, Ifra Saifi, Adam Bayless, William Wen, António Preto, Erik DeBloois, Jennifer Shipp, Tendai Chisowa, August Allen, Daniel Wee, Viswa Colluru, Biswapriya B. Misra, Andrew Katz","doi":"10.1021/acs.jnatprod.6c00498","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.6c00498","url":null,"abstract":"<p>Terpenoids are among the most chemically diverse natural product classes in the plant kingdom and are a source of numerous nature-inspired human medicines. One specific subclass, diterpenoids, defined by a C20 skeleton, includes attractive compounds such as the anticancer drug Taxol, the sweetener steviol, and the plant hormone gibberellin. One specialized group of <em>ent</em>-labdane (bicyclic) diterpenoids, primarily reported from the genus <em>Andrographis</em> (Acanthaceae), is the source of andrographolides, a diverse array of bioactive scaffolds with anti-inflammatory, antioxidant, anticancer, antimicrobial, and antihyperglycemic properties. Using high-throughput metabolomics, we set out to examine the molecular diversity within the Acanthaceae family, alongside other taxonomic lineages reported to accumulate diterpenoids. In a combined metabolomic investigation of 31 genera spanning Acanthaceae, Lamiaceae, and Poaceae, we annotated several reported andrographolide-type labdane diterpenoids and characteristic compounds unique to Acanthaceae. Integration of chemical, geographic, and taxonomic metadata with literature-driven assessments helped paint a chemotaxonomic and phylogeographic distribution map of andrographolide-type labdane diterpenoids across 163 countries. We found several species accumulate at least seven andrographolide-type compounds and another 17 labdane diterpenoids in our analysis. We conclude that labdane diterpenoid accumulation is more widespread, with multicontinental and shared evolutionary origins, than previously recognized.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"89 9","pages":"2436–2451"},"PeriodicalIF":3.7,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149152993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sesquiterpenoid Dimers from the Roots of Two Species of the Genus Inula with Cytotoxic Activity on Hepatocellular Carcinoma Cells","authors":"Feng Ju, Jianyu Xiang, Honghong Zhan, Yinda Qiu, Zhaoyue Dong, Fancheng Meng, Zhihua Liao, Min Chen","doi":"10.1021/acs.jnatprod.6c00758","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.6c00758","url":null,"abstract":"<p>Guided by the feature-based molecular networking approach, twenty-five previously undescribed sesquiterpenoid dimers (SDs) designated Inulaenoids A−Y (<strong>1−4</strong>, <strong>8−25</strong>, and <strong>27−29</strong>) along with four known analogues were isolated from the roots of <em>Inula helenium</em> L. and <em>Inula racemosa</em> Hook. f. Their structures and absolute configuration were unambiguously elucidated by spectroscopic data, X-ray diffraction, and theoretical calculations. Structurally, compounds <strong>1−19</strong> are rare SDs featuring two eudesmane units directly constructed through C−C bonds, including C-13−C-13′, C-13−C-11′, C-11−C-13′, and through a previously undescribed C-13−C-8′ connection. Fifteen compounds (<strong>3</strong>, <strong>4</strong>, <strong>10</strong>, <strong>15−18</strong>, <strong>20−23</strong> and <strong>25−28</strong>) showed potent cytotoxic activity to Huh-7 and HepG2 cells with the IC<sub>50</sub> values ranging from 1.9 ± 0.1 to 20.2 ± 0.3 μM. Among them, four compounds (<strong>3</strong>, <strong>4</strong>, <strong>10</strong> and <strong>17</strong>) displayed binding to proto-oncogenic c-Fos. Notably, compound <strong>17</strong> exhibited the highest binding affinity to recombinant human c-Fos, thereby activating <em>TP53</em> transcription and subsequently driving BAX/Bcl2-mediated apoptosis in liver cancer cells. Taken together, this study expands the structural diversity of sesquiterpenoid dimers from genus <em>Inula</em> as novel c-Fos-targeting lead compounds, providing new insights for the development of natural product-based anti-hepatocellular carcinoma agents.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"89 9","pages":"2656–2681"},"PeriodicalIF":3.7,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149153152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Marine Natural Product-Derived Tri-iodinated 2-Benzoylquinazolin-4(3H)-one Alkaloid as a Potent and Selective Agent against MRSA","authors":"Peng-Jie Li, Ji-Xiu Gao, Hao-Ran Li, Jing Sun, Cui-Fang Wang, Liu-Xia Lv, Mei-Yan Wei, Xin Liu, Jian-Yu Liu, Chang-Lun Shao","doi":"10.1021/acs.jnatprod.6c00727","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.6c00727","url":null,"abstract":"<p>Methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) poses a significant threat to global public health. Marine natural products provide a rich source of novel chemical entities for tackling MRSA infections. In this study, a series of halogenated 2-benzoylquinazolin-4(3<em>H</em>)-one derivatives (<strong>1−48</strong>) was designed and synthesized by innovatively integrating halogen pharmacophores with the biologically validated marine alkaloid penipanoid C. Anti-MRSA assays revealed that the introduction of iodine atoms significantly enhanced the activity of this class of compounds. Compound <strong>48</strong> (CHNQD-01748), bearing three iodine atoms, exhibited the most significant and selective antibacterial effect against the MRSA strain with an MIC value of 4 μg/mL against the reference MRSA strain (ATCC 43300) and 8−16 μg/mL against three clinical isolates. Further investigations revealed that <strong>48</strong> possessed a sustained antibacterial effect, potent biofilm-disrupting and biofilm-inhibitory activity, a long half-life, and a favorable preliminary safety profile in the models tested. An in vivo antibacterial assay demonstrated that <strong>48</strong> had vancomycin-comparable efficacy against localized MRSA skin infections yet provided superior suppression of systemic dissemination, inhibiting bacterial loads by >95% in the spleen, lung, and kidney. These findings showed the promising potential of <strong>48</strong> as a potent agent for the treatment of MRSA infections.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"89 9","pages":"2629–2642"},"PeriodicalIF":3.7,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149153142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hexacyclic 6/6/6/5/6/6 Spirosteroids Produced by a Marine-Derived Fungus Galactomyces pseudocandidus and Antifungal Activity against Candida Species","authors":"Hitoshi Kamauchi, Mikuru Kuroda, Mitsuaki Suzuki, Kanako Usui, Yuki Yatsui, Yuka Kiba, Masashi Kitamura, Yoshiaki Sugita","doi":"10.1021/acs.jnatprod.6c00038","DOIUrl":"10.1021/acs.jnatprod.6c00038","url":null,"abstract":"<p>Two spirosteroids, epoformsterols A and B (<strong>1</strong> and <strong>2</strong>), featuring a highly fused 6/6/6/5/6/6 hexacyclic framework, were isolated from the marine-derived fungus <em>Galactomyces pseudocandidus</em>. The structures of <strong>1</strong> and <strong>2</strong> were elucidated by NMR, HRMS, and single-crystal X-ray diffraction. The absolute configuration of <strong>1</strong> was established by comparison of calculated and experimental ECD spectra, and that of <strong>2</strong> was assigned by ECD comparison with <strong>1</strong>. Compounds <strong>1</strong> and <strong>2</strong> exhibited inhibitory activity against <em>Candida auris</em> and <em>C. albicans</em> with MIC values of 3.12−12.5 μg/mL, and MFC/MIC ratios suggested a fungistatic mode of action. Both compounds also inhibited <em>C. rugosa</em> lipase (CRL) in a model enzyme assay, with IC<sub>50</sub> values of 5.7 and 8.9 μM, respectively. These results identify a distinctive class of fungal steroids with antifungal activity.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"89 9","pages":"2429–2435"},"PeriodicalIF":3.7,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ryo Koyama, Nao Tanaka, Aki Ishiyama, Aoi Kimishima, Natsumi Watanabe, Shunta Hara, Yukihiro Asami, Arihiro Iwasaki, Mary Beth
{"title":"Lyngbyabellin Q, an Antimalarial Cyclic Peptide, and Its Acyclic Analog from a Cyanobacterial Biomat Dominated by Moorena sp.","authors":"Ryo Koyama, Nao Tanaka, Aki Ishiyama, Aoi Kimishima, Natsumi Watanabe, Shunta Hara, Yukihiro Asami, Arihiro Iwasaki, Mary Beth","doi":"10.1021/acs.jnatprod.6c00068","DOIUrl":"10.1021/acs.jnatprod.6c00068","url":null,"abstract":"<p>Two new lyngbyabellin analogs, Q (<strong>1</strong>) and R (<strong>2</strong>), were isolated from a marine cyanobacterial biomat dominated by <em>Moorena</em> sp. Their structures were established primarily by a combination of spectroscopic analyses and degradation reactions. Lyngbyabellin Q (<strong>1</strong>) inhibited the growth of HeLa cells and disrupted actin dynamics. In addition, lyngbyabellin Q (<strong>1</strong>) exhibited potent antimalarial activity with an IC<sub>50</sub> value of 22 nM, and a new structure−activity relationship enhancing selectivity for the growth inhibition of <em>Plasmodium falciparum</em> over mammalian cells was identified.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"89 9","pages":"59–65"},"PeriodicalIF":3.7,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emma K. Ellis, Laura P. Ióca, Jie Liu, Manyun Chen, Steven D. Bruner, Yousong Ding, Valerie J. Paul, Mohamed S. Donia, Hendrik Luesch
{"title":"Characterization of Dapalides D and E and Genomic Comparison of the Two Co-Occurring Dapalide-Producing Dapis spp.","authors":"Emma K. Ellis, Laura P. Ióca, Jie Liu, Manyun Chen, Steven D. Bruner, Yousong Ding, Valerie J. Paul, Mohamed S. Donia, Hendrik Luesch","doi":"10.1021/acs.jnatprod.6c00607","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.6c00607","url":null,"abstract":"<p>Marine cyanobacteria are a rich source of diverse bioactivenaturalproducts, targeting proteins involved in many diseases. Here, we combinedmetagenomic analysis to enhance the structure elucidation processof two new cyclodepsipeptides named dapalides D (<strong>1</strong>) andE (<strong>2</strong>) from a collection of a cyanobacterial mat containingmultiple <em>Dapis</em> species from Guam. Dapalides D/E arecomposed of 11 amino acids, including multiple identical units withdifferent configurations. Enantioselective amino acid identificationof the acid hydrolyzate established the identity of amino acids, includingthe configuration of α/β-stereogenic centers. Identificationand analysis of the dapalides D/E biosynthetic gene cluster from ametagenome-assembled genome aided the elucidation of α-configurationand establishment of the order of individual building blocks, collectivelyrevealing the total structure. Phylogenomic analysis indicates thatthe dapalides D/E producer belongs to <em>Dapis</em> sp. (<em>Dapis</em> sp. VPG23–80 MAG-2), which shares a 95.2% averagenucleotide identity with <em>Dapis</em> sp. VPG23–80MAG-1, the producer of dapalides A–C that cooccurs in the sameassemblage. Dapalide D (<strong>1</strong>) showed moderate growth inhibitoryactivity against various cancer cell lines. This work expands thedapalide structure class and further highlights the use of combinedchemical and metagenomic analyses for natural product structure elucidation.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"89 8","pages":"2373–2383"},"PeriodicalIF":3.7,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148858915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Curvulinic Acid–Gregatin Hybrids with Anti-inflammatory Activity from a Soil-Derived Fungus Penicillium sp. KYS-21","authors":"Du Chen, Xiang-Yu Liu, Ying Li, Chu-Hong Fang, Zhi-Pu Yu, Jin-Hai Yu, Jian-Min Yue","doi":"10.1021/acs.jnatprod.6c00492","DOIUrl":"10.1021/acs.jnatprod.6c00492","url":null,"abstract":"<p>Chemicalinvestigation of the fungus <em>Penicillium</em> sp. KYS-21 resulted in the isolation of 16 new curvulinic acid–gregatinhybrids (CAGHs), penicurgretides A–P (<strong>1</strong>–<strong>16</strong>), together with the only known analogue (<strong>17</strong>) of this rare class of natural products. Their structures were unambiguouslydetermined by comprehensive spectroscopic analyses, ECD calculations,single-crystal X-ray diffraction, and the modified Mosher’smethod. These hybrids exhibit remarkable diversity, featuring a conserved <em>R</em>-configuration at C-5 but variable stereochemistry at otherchiral centers. The α,β,γ,δ-unsaturated ketonein the C-5 side chain was established as a critical pharmacophore,as penicurgretides A (<strong>1</strong>) and G (<strong>7</strong>), bearingthis moiety, exhibited moderate anti-inflammatory activity with IC<sub>50</sub> values of 2.94 ± 0.54 and 3.50 ± 0.52 μM,respectively. Mechanistic studies revealed that penicurgretide A (<strong>1</strong>) suppresses inflammation through inhibition of the NF-κBand mitogen-activated protein kinase signaling pathways, with in vivoefficacy confirmed by reducing nitric oxide and ROS production inan LPS-induced zebrafish model. These findings expand the structuraldiversity of CAGHs and highlight penicurgretide A (<strong>1</strong>)as a promising lead for anti-inflammatory drug development.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"89 8","pages":"2275–2290"},"PeriodicalIF":3.7,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148409665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shengbin Jin, David F. Bruhn, Erica Burkman, Yovany Moreno, Angela A. Salim, Taizong Wu, Waleed M. Hussein, Robert J. Capon
{"title":"Craterstatins A–D: Terpenyl-p-aminobenzoic Acids Produced by an Australian Pasture Soil-Derived Streptomyces sp.","authors":"Shengbin Jin, David F. Bruhn, Erica Burkman, Yovany Moreno, Angela A. Salim, Taizong Wu, Waleed M. Hussein, Robert J. Capon","doi":"10.1021/acs.jnatprod.6c00473","DOIUrl":"10.1021/acs.jnatprod.6c00473","url":null,"abstract":"<p>An investigation into Australian pasture soil-derivedmicrobesled to the prioritization of <em>Streptomyces</em> sp. S4S-00182A09due to the media extract ability to inhibit the motility of dog heartworm <em>Dirofilaria immitis</em> microfilariae (Mf), and as asource of natural products with molecular formula unprecedented inthe scientific literature. Fractionation of a scaled-up cultivationextract of S4S-00182A09 yielded the new terpenyl-<em>p</em>-aminobenzoic acids, craterstatins A–D (<strong>1–4</strong>), together with the known fatty acid, 2-hydroxy-12-methylmyristicacid (<strong>5</strong>). Structures were assigned to <strong>1–5</strong> on the basis of spectroscopic, ECD, and Marfey’s analyses,as well as biosynthetic considerations and chemical transformation.Of note, craterstatin A (<strong>1</strong>) proved unstable to storageand handling, especially under acidic conditions, undergoing facileconversion to the stereoisomeric dehydration products craterstatinsB (<strong>2</strong>) and C (<strong>3</strong>) that feature an unprecedentedcarbo-heterocyclic framework, with <strong>3</strong> undergoing quantitativeconversion to <strong>2</strong> on storage. While the craterstatins <strong>1–4</strong> did not exhibit anthelmintic activity against <em>D. immitis</em> (EC<sub>50</sub> > 100 μM), weakactivity displayed by the hydroxylated fatty acid <strong>5</strong> promptedscreening of a library of synthetic hydroxy fatty acids <strong>6–11</strong>, which revealed modest inhibitory activity for (±)-3-hydroxyundecanoicacid (<strong>6</strong>), (±)-3-hydroxytetradecanoic acid (<strong>7</strong>), and (±)-3-hydroxypentadecanoic acid (<strong>8</strong>) (EC<sub>50</sub> 16.3, 28.2, and 19.0 μM, respectively).</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"89 8","pages":"2291–2299"},"PeriodicalIF":3.7,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148417036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fangjian Feng, Ran Wang, Zhiran Ju, Haixiao Jin, Zizhen Si, Yuxuan Mo, J. Enrico H. Lazaro, Wenhan Lin, C. Benjamin Naman, Bin Wu, Guanjun Yang, Shan He, and Lijian Ding
{"title":"Phenolmacrolide A, a Benzenoid Ansamycin from Marine-Derived Streptomyces olivaceus NBUA17 with In Vitro Antipancreatic Cancer Activity, Targets EEF1A2","authors":"Fangjian Feng, Ran Wang, Zhiran Ju, Haixiao Jin, Zizhen Si, Yuxuan Mo, J. Enrico H. Lazaro, Wenhan Lin, C. Benjamin Naman, Bin Wu, Guanjun Yang, Shan He, and Lijian Ding","doi":"10.1021/acs.jnatprod.6c00567","DOIUrl":"10.1021/acs.jnatprod.6c00567","url":null,"abstract":"<p>Ansamycins with diverse ring systems play an indispensablerolein the pharmaceutical industry. A novel 20-membered ester-incorporatingbenzenoid ansamycin, phenolmacrolide A (<strong>1</strong>), and a newnaphthalenoid ansamycin, olimycin I (<strong>2</strong>), were obtainedfrom the marine-derived <em>Streptomyces olivaceus</em> NBUA17 using a strategy of combining genome mining, SNAP-MS, andHSQC NMR interpretation tools. Furthermore, investigation of the putativeansamycin biosynthetic gene cluster suggested that the novel benzenoidansamycin scaffold of compound <strong>1</strong> could be formed in partby a hydroxylase and luciferase-like monooxygenase. Compound <strong>1</strong> exhibited moderate activity inhibiting proliferation, migration,and invasion against PANC-1 cells <em>in vitro</em> by inducingcell apoptosis and promoting cancer cell entry into G2/M phase, andinhibiting epithelial-mesenchymal transition. Further drug affinity-responsivetarget stability assay, molecular docking, cell thermal shift assay,and siRNA transfection identified EEF1A2 as a molecular target ofcompound <strong>1</strong> in PANC-1 cells. This study identifies anunprecedented subtype within the benzenoid ansamycin family, broadensthe structural and bioactive diversity of macrocyclic ansamycins,and underscores the potential of marine-derived actinomycetes as aprolific source of pharmacologically promising lead molecules.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"89 8","pages":"2332–2346"},"PeriodicalIF":3.7,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148443487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}